Our studies have demonstrated that aged persons with long-term urinary catheters in place are universally bacteriuric and that complications include fevers, bacteremias, and acute pyelonephritis. Patients dying in nursing homes with urinary catheters in place have a prevalence of acute pyelonephritis of 38% as compared with 5% of those without a catheter in place (p less than .005). A logical extension of our work, which includes adherence of bacteria to surfaces, is to examine the important next step leading to acute pyelonephritis: the invasion of the epithelium. We are using three critical experimental elements: 1) human renal tubular epithelial cell cultures; 2) a bank of well-characterized strains of pyelonephritogenic E. coli and 3) a non-obstructed mouse model of ascending acute pyelonephritis. Based upon preliminary data and well-studied invasive intestinal infections, we will test the following hypothesis: 1. That certain E. coli strains are internalized into the tubular epithelial cells. 2. That internalization is preceded by and is dependent upon adhesion to the epithelial cell surface by P. fimbria or other bacterial adhesins 3. That internalization occurs by phagocytosis, an energy- consuming process of the epithelial cell. 4. That certain E. coli can kill tubular epithelial cells. 5. That tubular cells from old persons. 6. That pyelonephritogenic E. coli attaches to, internalizes into, and/or kills tubular cells in higher numbers than non- pyelonephritogenic strains. 7. That vesico-ureteral reflux and/or urine obstruction obviates adhesion and internalization for entry of E. coli into the renal parenchyma.